tbuckley/cabot-search huggingface dataset:
MLX plays a key role in lipid and glucose metabolism in humans: Evidence from in vitro and in vivo studies
Authors: Shilpa R Nagarajan, Eilidh J Livingstone, Thomas Monfeuga, Lara C Lewis, Shahul Hameed Liyakath Ali, Anandhakumar Chandran, David J Dearlove, Matt J Neville, Lingyan Chen, Cyrielle Maroteau, Maxwell A Ruby, Leanne Hodson
Journal: Metabolism (2023)
Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: a prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial
Authors: Sarah Alexander, Anne Aupérin, Simon Bomken, Monika Csóka, Bernarda Kazanowska, Alan K Chiang, Mara Andres, Anne Uyttebroeck, G A Amos Burke, József Zsiros, Marta Pillon, Catherine M Bollard, Lara Mussolin, Jaime Verdu-Amoros, Bénédicte Neven, Donald A Barkauskas, Keith Wheatley, Catherine Patte, Thomas G Gross, Véronique Minard-Colin
Journal: The Lancet Haematology (2023)
Unmet needs and evidence gaps in hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis
Authors: Michael E. Wechsler, Bernhard Hellmich, Maria C. Cid, David Jayne, Xinping Tian, Lee Baylis, Florence Roufosse
Journal: Journal of Allergy and Clinical Immunology (2023)

Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) are rare systemic inflammatory disorders with overlapping symptoms, elevated eosinophil counts, and heterogenous clinical presentations. Although progress has been made in recent years, there are substantial gaps in our understanding of the pathologic mechanisms involved in these diseases, as well as numerous unmet needs relating to both diagnosis and patient management. For example, in most cases of HES, the underlying cause of hypereosinophilia is unknown, while in EGPA, although a polygenic genetic susceptibility has been found, understanding of the pathogenic mechanisms remains largely elusive. Delineating differences between certain disease variants may be challenging, and there are no reliable predictive markers of disease course. In addition, the current diagnostic criteria for HES and classification criteria for EGPA are not easy to implement in a nonspecialist setting, and specialist referral pathways need to be signposted more clearly. Furthermore, disease-specific activity scores need to be developed to aid the assessment of treatment effects, and improved biomarkers are needed to aid with treatment stratification. In this review, we outline the limitations of our current understanding of HES and EGPA and highlight areas for future work, which ultimately should help improve patient management and outcomes.
Loss of CEACAM1 in endothelial cells causes hepatic fibrosis
Authors: Harrison T. Muturi, Hilda E. Ghadieh, Raziyeh Abdolahipour, Hannah L. Stankus, Getachew Debas Belew, James K. Liu, Marziyeh Salehi Jahromi, Abraham D. Lee, Bernhard B. Singer, Isabella Angeli-Pahim, Tejasav S. Sehrawat, Harmeet Malhi, Stefaan Verhulst, Leo A. van Grunsven, Ali Zarrinpar, Sergio Duarte, Sonia M. Najjar
Journal: Metabolism (2023)
Using the ELF test, FIB-4 and NAFLD fibrosis score to screen the population for liver disease
Authors: Maria Kjaergaard, Katrine Prier Lindvig, Katrine Holtz Thorhauge, Peter Andersen, Johanne Kragh Hansen, Nanna Kastrup, Jane Møller Jensen, Camilla Dalby Hansen, Stine Johansen, Mads Israelsen, Nikolaj Torp, Morten Beck Trelle, Shan Shan, Sönke Detlefsen, Steen Antonsen, Jørgen Ellegaard Andersen, Isabel Graupera, Pere Ginés, Maja Thiele, Aleksander Krag
Journal: Journal of Hepatology (2023)
Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death: Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer
Authors: Sebastiaan Remmers, Chris H. Bangma, Rebecka A. Godtman, Sigrid V. Carlsson, Anssi Auvinen, Teuvo L.J. Tammela, Louis J. Denis, Vera Nelen, Arnauld Villers, Xavier Rebillard, Maciej Kwiatkowski, Franz Recker, Stephen Wyler, Marco Zappa, Donella Puliti, Giuseppe Gorini, Alvaro Paez, Marcos Lujan, Daan Nieboer, Fritz H. Schröder, Monique J. Roobol
Journal: European Urology (2023)

The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age.
Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis—a randomized controlled trial (PSORRO)
Authors: Mette Gyldenløve, Howraman Meteran, Jennifer A. Sørensen, Simon Fage, Yiqiu Yao, Jesper Lindhardsen, Christoffer V. Nissen, Tanja Todberg, Simon F. Thomsen, Lone Skov, Claus Zachariae, Lars Iversen, Mia-Louise Nielsen, Alexander Egeberg
Journal: The Lancet Regional Health - Europe (2023)

Roflumilast is a targeted inhibitor of phosphodiesterase (PDE)-4 and has been approved for treatment of severe chronic obstructive pulmonary disease for more than a decade. Generic versions are available in the United States. PDE-4 is involved in the psoriasis pathogenesis, but the efficacy and safety of oral roflumilast in patients with psoriasis have not previously been studied.A company-independent, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.govNCT04549870). Patients were randomized 1:1 to receive monotherapy with oral roflumilast 500 μg once daily or placebo. At week 12, placebo patients were switched to open-label roflumilast through week 24. The primary endpoint was a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI75) at week 12.In all, 46 patients were randomized (roflumilast, n = 23; placebo, n = 23). At week 12, significantly more patients in the active arm achieved PASI75 (8 of 23 patients [35%]) vs. placebo (0 of 23 patients [0%], with a difference vs. placebo of 8 [35%] patients, 95% CI: 3 [13%]-13 [57%] patients) (p = 0.014). At week 24, 15 (65%), 10 (44%), 5 (22%), and 2 (9%) of patients treated with roflumilast from week 0 had PASI50, PASI75, PASI90, and PASI100 responses (key secondary endpoints), respectively. The most prevalent, drug-related adverse events in both treatment groups were transient gastrointestinal symptoms, weight-loss, headache, and insomnia. A total of three patients (roflumilast n = 2; placebo, n = 1) discontinued therapy due to adverse events.Oral roflumilast was efficacious and safe in treating moderate-to-severe plaque psoriasis over 24 weeks. With generic versions available, this drug may represent an inexpensive and convenient alternative to established systemic psoriasis treatments.Financial support was received from Herlev and Gentofte Hospital, University of Copenhagen, and independent grants from private foundations in Denmark. No pharmaceutical company, including the market authorization holder of roflumilast, was involved in the study at any point.
Hepatocytes undergo punctuated expansion dynamics from a periportal stem cell niche in normal human liver
Authors: Adam M. Passman, Magnus J. Haughey, Emanuela Carlotti, Marc J. Williams, Bianca Cereser, Meng-Lay Lin, Shruthi Devkumar, Jonathan P. Gabriel, Enrico Gringeri, Umberto Cillo, Francesco Paolo Russo, Matthew Hoare, Joanne ChinAleong, Marnix Jansen, Nicholas A. Wright, Hermant M. Kocher, Weini Huang, Malcolm R. Alison, Stuart A.C. McDonald
Journal: Journal of Hepatology (2023)

While normal human liver is thought to be generally quiescent, clonal hepatocyte expansions have been observed, though neither their cellular source nor their expansion dynamics have been determined. Knowing the hepatocyte cell of origin, and their subsequent dynamics and trajectory within the human liver will provide an important basis to understand disease-associated dysregulation.
Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus
Authors: Qing-Song Deng, Yuan Gao, Bi-Yu Rui, Xu-Ran Li, Po-Lin Liu, Zi-Yin Han, Zhan-Ying Wei, Chang-Ru Zhang, Fei Wang, Helen Dawes, Tong-He Zhu, Shi-Cong Tao, Shang-Chun Guo
Journal: Bioactive Materials (2023)

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH-M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration.
Identification of key opportunities for optimising the management of high-risk COPD patients in the UK using the CONQUEST quality standards: an observational longitudinal study
Authors: David M G Halpin, Andrew P Dickens, Derek Skinner, Ruth Murray, Mukesh Singh, Katherine Hickman, Victoria Carter, Amy Couper, Alexander Evans, Rachel Pullen, Shruti Menon, Tamsin Morris, Hana Muellerova, Mona Bafadhel, James Chalmers, Graham Devereux, Martin Gibson, John R Hurst, Rupert Jones, Konstantinos Kostikas, Jennifer Quint, Dave Singh, Marije van Melle, Tom Wilkinson, David Price
Journal: The Lancet Regional Health - Europe (2023)

This study compared management of high-risk COPD patients in the UK to national and international management recommendations and quality standards, including the COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST). The primary comparison was in 2019, but trends from 2000 to 2019 were also examined. Patients identified in the Optimum Patient Care Research Database were categorised as newly diagnosed (≤12 months after diagnosis), already diagnosed, and potential COPD (smokers having exacerbation-like events). High-risk patients had a history of ≥2 moderate or ≥1 severe exacerbations in the previous 12 months. For diagnosed patients, the median time between diagnosis and first meeting the high-risk criteria was 617 days (Q1-Q3: 3246). The use of spirometry for diagnosis increased dramatically after 2004 before plateauing and falling in recent years. In 2019, 41% (95% CI 39–44%; n = 550/1343) of newly diagnosed patients had no record of spirometry in the previous year, and 45% (95% CI 43–48%; n = 352/783) had no record of a COPD medication review within 6 months of treatment initiation or change. In 2019, 39% (n = 6893/17,858) of already diagnosed patients had no consideration of exacerbation rates, 46% (95% CI 45–47%; n = 4942/10,725) were not offered or referred for pulmonary rehabilitation, and 41% (95% CI 40–42%; n = 3026/7361) had not had a COPD review within 6 weeks of respiratory hospitalization. Opportunities for early diagnosis of COPD patients at high risk of exacerbations are being missed. Newly and already diagnosed patients at high-risk are not being assessed or treated promptly. There is substantial scope to improve the assessment and treatment optimisation of these patients. This study is conducted by the Observational & Pragmatic Research International Ltd and was co-funded by Optimum Patient Care and AstraZeneca. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.
Nucleic acid biomarkers of immune response and cell and tissue damage in children with COVID-19 and MIS-C
Authors: Conor J. Loy, Alicia Sotomayor-Gonzalez, Venice Servellita, Jenny Nguyen, Joan Lenz, Sanchita Bhattacharya, Meagan E. Williams, Alexandre P. Cheng, Andrew Bliss, Prachi Saldhi, Noah Brazer, Jessica Streithorst, William Suslovic, Charlotte J. Hsieh, Burak Bahar, Nathan Wood, Abiodun Foresythe, Amelia Gliwa, Kushmita Bhakta, Maria A. Perez, Laila Hussaini, Evan J. Anderson, Ann Chahroudi, Meghan Delaney, Atul J. Butte, Roberta L. DeBiasi, Christina A. Rostad, Iwijn De Vlaminck, Charles Y. Chiu
Journal: Cell Reports Medicine (2023)

Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here, we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with COVID-19 or MIS-C across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between COVID-19 and MIS-C, with increased multiorgan involvement in MIS-C encompassing diverse cell types, including endothelial and neuronal cells, and an enrichment of pyroptosis-related genes. Whole-blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C but also MIS-C-specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole-blood RNA in paired samples yields different but complementary signatures for each disease state. Our work provides a systems-level view of immune responses and tissue damage in COVID-19 and MIS-C and informs future development of new disease biomarkers.
Genetic subdivisions of follicular lymphoma defined by distinct coding and noncoding mutation patterns
Authors: Kostiantyn Dreval, Laura K. Hilton, Manuela Cruz, Haya Shaalan, Susana Ben-Neriah, Merrill Boyle, Brett Collinge, Krysta M. Coyle, Gerben Duns, Pedro Farinha, Bruno M. Grande, Barbara Meissner, Prasath Pararajalingam, Christopher K. Rushton, Graham W. Slack, Jasper Wong, Andrew J. Mungall, Marco A. Marra, Joseph M. Connors, Christian Steidl, David W. Scott, Ryan D. Morin
Journal: Blood (2023)

Follicular lymphoma (FL) accounts for ∼20% of all new lymphoma cases. Increases in cytological grade are a feature of the clinical progression of this malignancy, and eventual histologic transformation (HT) to the aggressive diffuse large B-cell lymphoma (DLBCL) occurs in up to 15% of patients. Clinical or genetic features to predict the risk and timing of HT have not been described comprehensively. In this study, we analyzed whole-genome sequencing data from 423 patients to compare the protein coding and noncoding mutation landscapes of untransformed FL, transformed FL, and de novo DLBCL. This revealed 2 genetically distinct subgroups of FL, which we have named DLBCL-like (dFL) and constrained FL (cFL). Each subgroup has distinguishing mutational patterns, aberrant somatic hypermutation rates, and biological and clinical characteristics. We implemented a machine learning-derived classification approach to stratify patients with FL into cFL and dFL subgroups based on their genomic features. Using separate validation cohorts, we demonstrate that cFL status, whether assigned with this full classifier or a single-gene approximation, is associated with a reduced rate of HT. This implies distinct biological features of cFL that constrain its evolution, and we highlight the potential for this classification to predict HT from genetic features present at diagnosis.
Machine learning identifies clusters of longitudinal autoantibody profiles predictive of systemic lupus erythematosus disease outcomes
Authors: May Yee Choi, Irene Chen, Ann Elaine Clarke, Marvin J Fritzler, Katherine A Buhler, Murray Urowitz, John Hanly, Yvan St-Pierre, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Sasha Bernatsky, Daniel J Wallace, David Alan Isenberg, Anisur Rahman, Joan T Merrill, Paul R Fortin, Dafna D Gladman, Ian N Bruce, Michelle Petri, Ellen M Ginzler, Mary Anne Dooley, Rosalind Ramsey-Goldman, Susan Manzi, Andreas Jönsen, Graciela S Alarcón, Ronald F van Vollenhoven, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, Kenneth Kalunian, Søren Jacobsen, Christine Peschken, Diane L Kamen, Anca Askanase, Jill P Buyon, David Sontag, Karen H Costenbader
Journal: Annals of the Rheumatic Diseases (2023)

A novel longitudinal clustering technique was applied to comprehensive autoantibody data from a large, well-characterised, multinational inception systemic lupus erythematosus (SLE) cohort to determine profiles predictive of clinical outcomes.
Models of the cerebellum and motor learning
Authors: James C. Houk, Jay T. Buckingham, Andrew G. Barto
Journal: Behavioral and Brain Sciences (1996)

This article reviews models of the cerebellum and motor learning, from the landmark papers by Marr and Albus through those of the present time. The unique architecture of the cerebellar cortex is ideally suited for pattern recognition, but how is pattern recognition incorporated into motor control and learning systems? The present analysis begins with a discussion of exactly what the cerebellar cortex needs to regulate through its anatomically defined projections to premotor networks. Next, we examine various models showing how the microcircuitry in the cerebellar cortex could be used to achieve its regulatory functions. Having thus defined what it is that Purkinje cells in the cerebellar cortex must learn, we then evaluate theories of motor learning. We examine current models of synaptic plasticity, credit assignment, and the generation of training information, indicating how they could function cooperatively to guide the processes of motor learning.
TCTAP C-103 A Case of Coronary Artery Dissection and Perforation in a Severe Three Vessel Coronary Artery Disease With Chronic Total Occlusion
Authors: Simeon Villangca, Patrick Nuique Vera Cruz, Myrtle Shekinah Lopez-Cayco, Glein Sayat, Ronald Santos, Alwyn Susanto, Francisco Dalangin
Journal: Journal of the American College of Cardiology (2023)
NHS psychologist died after rare reaction to AstraZeneca vaccine, rules coroner
Authors: Clare Dyer
Journal: BMJ (2023)

NHS psychologist died after rare reaction to AstraZeneca vaccine, rules coroner Clare DyerA "fit and healthy" NHS clinical psychologist who was among the first to be given the AstraZeneca covid-19 vaccine in January 2021 died because of a rare reaction to it, a coroner has ruled.1
A Highly Energy-Efficient Body-Coupled Transceiver Employing a Power-on-Demand Amplifier
Authors: Tao He, Yabin Zheng, Xu Liang, Jiamin Li, Longyang Lin, Wenfeng Zhao, Yongfu Li, Jian Zhao
Journal: Cyborg and Bionic Systems (2023)

Wearable body sensor nodes require massive data transmission under limited energy. However, it suffers from drastically varying channel loss, which limits its energy efficiency in practical scenarios. This paper presents a power-driven body-channel transceiver (TRX), whose power consumption can be adaptively tuned against varying channel loss. An out-band programmable gain amplifier (PGA) is proposed to save power and generate a quasi-linear correlation between PGA gain and power. By using the quasi-linear gain-power relationship, we propose an auto gain/power control technique to realize on-demand power consumption. In addition, a differential balanced transmitter is designed to eliminate base-band harmonics in on-off keying modulation and increase the power delivered by the transmitter (TX). The TX and receiver (RX) of the prototype were integrated into 1 chip and fabricated in a 55-nm complementary metal oxide semiconductor process. During the measurement, 2 chips were configured as TX and RX, respectively. Both the TX and the RX were wearable, powered by lithium batteries, and attached to the subject’s hands. The prototype achieved a 5.25-Mbps data rate with 16-pJ/bit energy efficiency at a 1.5-m straight-line ground path distance. Furthermore, the proposed TRX maintained stable communication within a 1.5-m distance, while dynamically reducing power consumption.
Publisher Correction: FIPRESCI: droplet microfluidics based combinatorial indexing for massive-scale 5′-end single-cell RNA sequencing
Authors: Yun Li, Zheng Huang, Zhaojun Zhang, Qifei Wang, Fengxian Li, Shufang Wang, Xin Ji, Shaokun Shu, Xiangdong Fang, Lan Jiang
Journal: Genome biology (2023)
TCTAP A-003 Optical Coherence Tomography Findings of High-Risk Plaques on Coronary Computed Tomography Angiography
Authors: Daisuke Kinoshita, Keishi Suzuki, Yoshiyasu Minami, Tomoyo Sugiyama, Haruhito Yuki, Takayuki Niida, Hang Lee, Iris McNulty, Tsunekazu Kakuta, Maros Ferencik, Ik-Kyung Jang
Journal: Journal of the American College of Cardiology (2023)
Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer’s disease
Authors: Christopher Daniel Morrone, Radha Raghuraman, S. Abid Hussaini, Wai Haung Yu
Journal: Molecular Neurodegeneration (2023)

Abstract Failed proteostasis is a well-documented feature of Alzheimer’s disease, particularly, reduced protein degradation and clearance. However, the contribution of failed proteostasis to neuronal circuit dysfunction is an emerging concept in neurodegenerative research and will prove critical in understanding cognitive decline. Our objective is to convey Alzheimer’s disease progression with the growing evidence for a bidirectional relationship of sleep disruption and proteostasis failure. Proteostasis dysfunction and tauopathy in Alzheimer’s disease disrupts neurons that regulate the sleep–wake cycle, which presents behavior as impaired slow wave and rapid eye movement sleep patterns. Subsequent sleep loss further impairs protein clearance. Sleep loss is a defined feature seen early in many neurodegenerative disorders and contributes to memory impairments in Alzheimer’s disease. Canonical pathological hallmarks, β-amyloid, and tau, directly disrupt sleep, and neurodegeneration of locus coeruleus, hippocampal and hypothalamic neurons from tau proteinopathy causes disruption of the neuronal circuitry of sleep. Acting in a positive-feedback-loop, sleep loss and circadian rhythm disruption then increase spread of β-amyloid and tau, through impairments of proteasome, autophagy, unfolded protein response and glymphatic clearance. This phenomenon extends beyond β-amyloid and tau, with interactions of sleep impairment with the homeostasis of TDP-43, α-synuclein, FUS, and huntingtin proteins, implicating sleep loss as an important consideration in an array of neurodegenerative diseases and in cases of mixed neuropathology. Critically, the dynamics of this interaction in the neurodegenerative environment are not fully elucidated and are deserving of further discussion and research. Finally, we propose sleep-enhancing therapeutics as potential interventions for promoting healthy proteostasis, including β-amyloid and tau clearance, mechanistically linking these processes. With further clinical and preclinical research, we propose this dynamic interaction as a diagnostic and therapeutic framework, informing precise single- and combinatorial-treatments for Alzheimer’s disease and other brain disorders. Graphical Abstract
Understanding the activity of antibody–drug conjugates in primary and secondary brain tumours
Authors: Maximilian J. Mair, Rupert Bartsch, Emilie Le Rhun, Anna S. Berghoff, Priscilla K. Brastianos, Javier Cortes, Hui K. Gan, Nancy U. Lin, Andrew B. Lassman, Patrick Y. Wen, Michael Weller, Martin van den Bent, Matthias Preusser
Journal: Nature Reviews Clinical Oncology (2023)
Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial
Authors: Sant-Rayn Pasricha, Martin N Mwangi, Ernest Moya, Ricardo Ataide, Glory Mzembe, Rebecca Harding, Truwah Zinenani, Leila M Larson, Ayse Y Demir, William Nkhono, Jobiba Chinkhumba, Julie A Simpson, Danielle Clucas, William Stones, Sabine Braat, Kamija S Phiri
Journal: The Lancet (2023)